The Chalcone Lonchocarpin Inhibits Wnt/β-Catenin Signaling and Suppresses Colorectal Cancer Proliferation

Predes, Danilo; Oliveira, Luiz F. S.; Ferreira, Laís S. S.; Maia, Lorena A.; Delou, João Marcos de Azevedo; Faletti, Anderson; Oliveira, Igor Silva; Amado, Nathália G.; Reis, Alice H.; Fraga, Carlos A.M.; Kuster, Ricardo Machado; Mendes, Fábio A.; Borges, Helena L.; Abreu, José G.

doi:10.3390/cancers11121968

Cited by 40 publications

(35 citation statements)

References 48 publications

(40 reference statements)

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“…The azoxymethane/dextran sodium sulfate (AOM/DSS) mouse model stands as a relevant preclinical inflammation-associated CRC model with histological and phenotypic features. AOM/DSS simulates the physiological and pathological process of cancer induced by chronic intestinal inflammation, and therefore, it has been widely used to study the formation mechanism of inflammation-related cancer ( 15 , 16 ). The purpose of this study was to study the antitumor effect of a microecological preparation, JK5G, by constructing the tumor model.…”

Section: Introductionmentioning

confidence: 99%

Inhibitory Effect of a Microecological Preparation on Azoxymethane/Dextran Sodium Sulfate-Induced Inflammatory Colorectal Cancer in Mice

Zhang

Chen

et al. 2020

Front. Oncol.

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This study aims to investigate the antitumor effect and the possible mechanism of a microecological preparation (JK5G) in mice. The mice treated with AOM/DSS were then randomly divided into the two model groups and the JK5G group, and the blank control group was included. Fecal samples were used for liquid chromatographymass spectrometry and 16S rRNA gene sequencing analyses to reveal metabolic perturbations and gut flora disorders to demonstrate the effects of JK5G. Compared with the mice in the control group, the weight and food intake of mice after JK5G treatment were both upregulated. Moreover, JK5G could inhibit the growth of colon tumors and prolong the survival rate of mice, as well as inhibit the levels of cytokines in serum. The proportions of lymphocytes, T cells, CD3 + CD4 + T cells, and CD3 + CD8 + T cells in the spleen of the JK5G mice were all significantly increased compared to those in the control group (p < 0.05). Similarly, compared with the model group, the proportions of lymphocytes, B cells, T cells, natural killer T cells, CD3 + CD4 + T cells, and CD3 + CD8 + T cells in the intestinal tumors of the JK5G mice were significantly increased (p < 0.05). Furthermore, 16S rRNA high-throughput sequencing data revealed that Alloprevotella in the JK5G group was significantly upregulated, and Ruminiclostridium, Prevotellaceae_UCG_001, and Acetitomaculum were significantly downregulated. Fecal and serum metabolite analysis detected 939 metabolites, such as sildenafil and pyridoxamine, as well as 20 metabolites, including N-Palmitoyl tyrosine and dihydroergotamine, which were differentially expressed between the JK5G and model groups. Integrated analysis of 16s rRNA and metabolomics data showed that there were 19 functional relationship pairs, including 8 altered microbiota, such as Ruminiclostridium and Prevotellaceae_UCG_001, and 16 disturbed metabolites between the JK5G and model groups. This study revealed that JK5G treatment

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Section: Introductionmentioning

confidence: 99%

Inhibitory Effect of a Microecological Preparation on Azoxymethane/Dextran Sodium Sulfate-Induced Inflammatory Colorectal Cancer in Mice

Zhang

Chen

et al. 2020

Front. Oncol.

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“…28 And growing researches suggested that wnt/β-catenin was involved in the growth and metastasis of tumor cells. [29][30][31] As well, activation of wnt/ β-catenin pathway was found in glioma cells, and blocking of wnt/β-catenin pathway suppressed multiple oncogenic targets. 32 In our study, forced expression of FGD5-AS1 activated wnt/β-catenin pathway with a dramatic change of β-catenin and cyclin D1.…”

Section: Discussionmentioning

confidence: 99%

<p>Long Noncoding RNA FGD5-AS1 Promotes Glioma Cell Proliferation, Migration and Invasion by Regulating wnt/β-Catenin Pathway</p>

Zhao¹,

Xue²,

Zhang³

et al. 2020

CMAR

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Purpose: To investigate the specific function of long noncoding RNA FGD5 antisense RNA 1 (lncRNA FGD5-AS1) in glioma. Materials and Methods: The level of FGD5-AS1 was detected in clinical samples and cell lines by qRT-PCR. Small interfering RNA (siRNA) of FGD5-AS1 or scramble siRNA was transfected into U87 cell lines to examine the role of FGD5-AS1 on glioma development. The proliferation of glioma cells was tested by Cell Counting Kit-8 (CCK-8), the migration and invasion of glioma cells were tested by transwell assay without matrigel or with matrigel. Western blot was used to detect the protein expression, and XAV-939 was used to inhibit wnt/β-catenin pathway. The effect of FGD5-AS1 on tumorigenesis of glioma was confirmed by xenograft nude mice model. Results: FGD5-AS1 was significantly increased in glioma tissues and cells. Loss of FGD5-AS1 inhibited the proliferation, migration and invasion of U87 cells. Furthermore, overexpression of FGD5-AS1 increased the mRNA and protein levels of β-catenin and cyclin D1. Blocking of wnt/β-catenin using XAV-939 reversed the promotion role of FGD3-AS1 on glioma cells' migration and invasion. The in vivo tumor growth assay showed that FGD3-AS1 accelerated glioma tumorigenesis with activating wnt/β-catenin pathway. Conclusion: Our research emphasized FGD5-AS1 acting as an oncogene by regulating wnt/ β-catenin signaling pathway, thus providing some novel experimental basis for clinical treatment of glioma.

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“…IEC-6 cells have been widely used in the study of intestinal mucosal repair [22]. Scholars have conducted in-depth and systematic research on the physiological regulation [23], signaling pathways [24] and pathology [25] of intestinal mucosal injury, but there have been few reports of drugs to repair the gastrointestinal mucosa. This study demonstrated that GE can promote the migration of IEC-6 cells and reduce LPSinduced damage and has a protective effect on IEC-6 cells.…”

Section: Discussionmentioning

confidence: 99%

Geniposide, a component of Gardenia jasminoides Ellis, inhibits NF-ĸB to attenuate LPS-induced injury in intestinal epithelial cells

Cui¹,

Qiao²,

Qiu-ju³

et al. 2020

Preprint

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Background: The nuclear factor-ĸB (NF-ĸB) transcriptional system is a major effector pathway involved in inflammatory responses. Previous studies found that a Gardenia decoction (GD) inhibited the expression of NF-κB in a lipopolysaccharide (LPS)-stimulated mouse intestinal injury model. Herein, we hypothesized that geniposide (GE), a component of Gardenia jasminoides Ellis, also exerts anti-inflammatory effects and inhibits NF-ĸB activity in LPS-induced intestinal epithelial cells (IEC-6). IEC-6 cells were stimulated with LPS, following which the effects of GE on NF-ĸB signaling in the IEC-6 cells were examined by western blotting to detect IĸB phosphorylation/degradation. The expression of NF-κB was determined by immunofluorescence assay (IFA). Enzyme-linked immunosorbent assay (ELISA) was used to detect the inhibitory effect of GE on the release of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) activated by LPS in IEC-6 cells. In addition, the migration ability of IEC-6 cells was observed by the scratch method. Results: These results showed that GE dose-dependently downregulated levels of the proinflammatory cytokines TNF-α, IL-6 and IL-1β that had been upregulated by LPS and suppressed the phosphorylation of IĸB and NF-ĸB induced by LPS. Our findings indicated that GE could reduce LPS-induced NF-ĸB signaling and proinﬂammatory expression in IEC-6 cells and significantly enhance the migration of IEC-6 cells. Moreover, GE inhibited the expression of NF-κB, nuclear transfer, and transcriptional activity in IEC-6 cells. Conclusion: GE could block the synthesis of inflammatory factors of IEC-6 cells by inhibiting activation of the IĸB/NF-κB signaling pathway induced by LPS.

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The Chalcone Lonchocarpin Inhibits Wnt/β-Catenin Signaling and Suppresses Colorectal Cancer Proliferation

Cited by 40 publications

References 48 publications

Inhibitory Effect of a Microecological Preparation on Azoxymethane/Dextran Sodium Sulfate-Induced Inflammatory Colorectal Cancer in Mice

Inhibitory Effect of a Microecological Preparation on Azoxymethane/Dextran Sodium Sulfate-Induced Inflammatory Colorectal Cancer in Mice

<p>Long Noncoding RNA FGD5-AS1 Promotes Glioma Cell Proliferation, Migration and Invasion by Regulating wnt/β-Catenin Pathway</p>

Geniposide, a component of Gardenia jasminoides Ellis, inhibits NF-ĸB to attenuate LPS-induced injury in intestinal epithelial cells

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